Abstract
Inhibition of Escherichia Coli (E. coli) cell division, when exposed to electrolysis products from a platinum electrode, was first reported by Rosenberg et al. [3]. This same group subsequently studied several ammonium platinum salts in transplanted Sarcoma 180 ([4]) and found some of these platinum salts were capable of inhibiting tumor growth significantly in this animal model system. Later, other investigators confirmed the activity of platinum salts in a wide variety of transplanted rodent tumor models. The most consistently potent analog, cis-platinum(II) diamminedichloride (cis-Pt(II)), was selected for extensive toxicological studies in rodents, dogs, and monkeys to determine preclinical toxic effects. The highest nontoxic dose for dogs was 3.87 mg/m2/d × 5 days. Monkeys appeared to be somewhat more sensitive, with the highest nontoxic dose being 1.94 mg/m2/d × 5 days. However, the lethal dose for both dogs and monkeys was similar; 31.3 mg/m2 for the former and 33.6 mg/m2 for the latter. At the higher doses, the major sites involved in animal toxicological studies were kidney, gastrointestinal tract, lymphatics, and the bone marrow. As a result of these studies and reports, a Phase I clinical trial was started under the auspices of the Southwest Cancer Chemotherapy Study Group (SWCCSG) in June of 1971.
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References
Harder, H. C.: Molecular effects of tumor inhibiting compounds in mammalian cells: Investigations into their possible mechanisms of action. Thesis, Michigan State University, East Lansing, 1970.
Howle, Jerry, A., Gale, Glen, R., Smith, Alayne, B.: A proposed mode of action of antitumor platinum compounds based upon studies with cis-dichloro-([G-3H]dipyridine) platinum(II). Biochem. Pharmacol. 21, 1465 (1972).
Rosenberg, B., van Camp, L., Krigas, T.: Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature (Lond.) 205, 698 (1965).
Rosenberg, B., van Camp, L., Trosko, J. E., Mansour, V. H.: Platinum compounds: a new class of potent antitumor agents. Nature (Lond.) 222, 385 (1969).
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© 1974 Springer-Verlag Berlin · Heidelberg
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Talley, R.W., O’bryan, R.M., Gutterman, J., Brownlee, R.W., McCredie, K.B. (1974). Clinical Evalutions of Toxic Effects of cis-Platinum (II) Diamminedichloride. In: Connors, T.A., Roberts, J.J. (eds) Platinum Coordination Complexes in Cancer Chemotherapy. Recent Results in Cancer Research, vol 48. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-49306-5_12
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DOI: https://doi.org/10.1007/978-3-642-49306-5_12
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-49308-9
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